Topical review on nano-vaccinology: Biochemical promises and key challenges.

Nanomaterials have wide-ranging biomedical applications in prevention, treatment and control of diseases. Nanoparticle based vaccines have proven prodigious prophylaxis of various infectious and non-infectious diseases of human and animal concern. Nano-vaccines outnumber the conventional vaccines by virtue of plasticity in physio-chemical properties and ease of administration. The efficacy of nano-based vaccines may be attributed to the improved antigen stability, minimum immuno-toxicity, sustained release, enhanced immunogenicity and the flexibility of physical features of nanoparticles. Based on these, the nano-based vaccines have potential to evoke both cellular and humoral immune responses. Targeted and highly specific immunological pathways required for solid and long lasting immunity may be achieved with specially engineered nano-vaccines. This review presents an insight into the prevention of infectious diseases (of bacterial, viral and parasitic origin) and non-infectious diseases (cancer, auto-immune diseases) using nano-vaccinology. Additionally, key challenges to the effective utilization of nano-vaccines from bench to clinical settings have been highlighted as research domains for future.

Sensitivity of SARS-CoV-2 antibody tests with late convalescent sera.

SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS-CoV-2 infection at later time points. To examine if the diagnostic sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 53 sera obtained 6 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.3% (95% confidence interval (CI) 84.3-98.8%), 98.1 % (95% CI: 89.9-100%) and 100 % (95% CI: 93.3-100%). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 45.3 % (95% CI: 31.6-59.6%) and 83.3% (95% CI: 70.2-91.9%). The nucleoprotein-based Roche and the glycoprotein-based Abbott receptor binding domain (RBD) and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests (p = 0.0001 to p = 0.039). The N-based Abbott antibody test was less sensitive 6 months than 4-10 weeks after SARS-CoV-2 infection (p = 0.0001). The findings show that most SARS-CoV-2 antibody assays correctly identified previous infection 6 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost diagnostic sensitivity over time.

PEG allergy - A COVID-19 pandemic-made problem? A German perspective.

Background: Polyethylene glycol (PEG) has been used for decades, but only caused allergic reactions exceptionally. Introduction of PEG-containing COVID-19 vaccines might have fostered public interest beyond medical reasoning. Objectives: To investigate the impact of the SARS-CoV-2 pandemic on the public interest in PEG allergy in Germany and the published PEG allergy cases worldwide. Methods: A retrospective longitudinal study was conducted to measure public interest in PEG allergy analyzing Google search volume in Germany from February 2018 to January 2022. Medically confirmed "PEG allergy" cases were analyzed by looking at the numbers of PubMed case reports and case series from 1977 until January 2022. Results: Web results in Germany before COVID-19 show search volumes related to "PEG allergy/testing" was negligible, with 10 search queries per month. The pandemic led to a >200-fold increase from 250 queries 2 years before to 55 720 queries 2 years thereafter, reflecting tremendous public interest. Additionally, the maximum monthly search volume from before to during the pandemic increased immensely for "vaccination" (57-fold), "vaccination and adverse effects" (85-fold), "vaccination and allergy" (71-fold). In contrast, the increase of publication numbers for the search term "PEG allergy" was small from 2019 to 2021 (2.5-fold). Only a very low number of 211 cases with "PEG allergy" worldwide since 1977 could be identified. Conclusion: PEG allergy became a topic of major public interest because of COVID-19 vaccination. Scientific publications have increased to a lesser extent, probably promoted by public awareness. Conversely, the overall number of cases published with PEG allergy remain very low. The current high demand for COVID-19 vaccination allergy testing is triggered by public interest instead of medical reasoning.

Applicability of on-site disinfection of personal protective equipment by ozone gas.

On-site disinfection techniques are beneficial during a pandemic when there is a marked shortage of personal protective equipment (PPE), as experienced during the coronavirus disease 2019 outbreak. Ozone gas has been considered an alternative on-site disinfectant during a pandemic because it has antimicrobial activities, can be produced from air by electricity without the need for storage, and can be easily deactivated after use. However, ozone gas might become distributed at the lower layer because it has a larger molecular weight than air. This study aimed to reveal the applicability of ozone gas for the on-site disinfection of PPE. The lockers meant for changing dresses were used as ozone gas exposure boxes, and the distribution of ozone was assayed. Considering that the determined ozone levels were not consistent in the types of ozone analysers, we studied the chemical and biological activities of ozone, which were evenly detected in the locker. The gown in the locker was also uniformly exposed to ozone. Results showed that ozone gas could be used for the on-site disinfection of PPE in a closed box, such as a locker. This finding is valuable during a pandemic when PPE is in short supply.

Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system. ACE2 is present as membrane-bound on several cell types, including the mucosa of the upper respiratory and of the gastrointestinal tracts, the endothelium, the platelets, and in soluble form in the plasma. The ACE2 enzyme converts the vasoconstrictor angiotensin II into peptides with vasodilator properties. Here we review the pathways for immunization and the molecular mechanisms through which the Spike protein, either from SARS-CoV-2 or encoded by the mRNA-based vaccines, interferes with the Renin-Angiotensin-System governed by ACE2, thus altering the homeostasis of the circulation and of the cardiovascular system. Understanding the molecular interactions of the Spike protein with ACE2 and the consequent impact on cardiovascular system homeostasis will direct the diagnosis and therapy of the vaccine-related adverse effects and provide information for development of a personalized vaccination that considers pathophysiological conditions predisposing to such adverse events.

An observational multi-centric COVID-19 sequelae study among health care workers.

Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

Efficacy and mechanisms of mobile application-delivered Acceptance and Commitment Therapy for posttraumatic stress disorder in China: Study protocol for a randomized controlled trial.

Background: As a result of the COVID-19 pandemic and its far-reaching impact, the prevalence of posttraumatic stress disorder (PTSD) symptoms is increasing significantly in China. Yet access to reliable and effective psychological treatment is still limited during the pandemic. The widespread adoption of mobile technologies may provide a new way to address this gap. In this research we will develop an Acceptance and Commitment Therapy (ACT) based intervention delivered by mobile application and will test its usability, efficacy, and mechanism of its effects in relieving PTSD symptoms. Methods: A total of 147 Chinese participants with a diagnosis of PTSD according to the Clinician Administered PTSD Scale (CAPS-5) will be randomly assigned to an intervention group (app-delivered ACT), an active comparison group (app-delivered mindfulness), or a waitlist group. Participants in the intervention group or comparison group will use their respective apps for one month. Online self-report questionnaires will be used to assess the primary outcome of PTSD symptoms and the secondary outcomes symptoms of depression, symptoms of anxiety, and posttraumatic growth. The potential mediating variable to be tested is psychological flexibility and its components. These assessments will be conducted at baseline, at five times during treatment, at the end of treatment, and at 1- and 3-month follow-ups. Discussion: As far as we know, this study is the first randomized controlled trial to investigate the usability, efficacy, and mechanism of an app-delivered ACT intervention for PTSD. Furthermore, the research will assess the effect of treatment in reducing dropout rates, explore effective therapeutic components, and investigate mechanisms of symptom change, which will be valuable in improving the efficacy and usability of PTSD interventions.Trial registration: ChiCTR2200058408.

Identification of alkaloids from Justicia adhatoda as potent SARS CoV-2 main protease inhibitors: An in silico perspective.

The COVID-19 pandemic, caused by SARS CoV-2, is responsible for millions of death worldwide. No approved/proper therapeutics is currently available which can effectively combat this outbreak. Several attempts have been undertaken in the search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro), key component for the cleavage of the viral polyprotein, is considered to be one of the important drug targets for treating COVID-19. Various phytochemicals, including polyphenols and alkaloids, have been proposed as potent inhibitors of Mpro. The alkaloids from leaf extracts of Justicia adhatoda have also been reported to possess anti-viral activity. But whether these alkaloids exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To explore this in detail, we have adopted computational approaches. Justicia adhatoda alkaloids possessing proper drug-likeness properties and two anti-HIV drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only one alkaloid (anisotine) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.9 kcal/mol). Molecular dynamic simulations (100 ns) revealed that Mpro-anisotine complex is more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bonds and MM-GBSA analysis suggested that anisotine is a more potent Mpro inhibitor than the two previously recommended antiviral drugs (lopinavir and darunavir) and may evolve as a promising anti-COVID-19 drug if proven in animal experiments and on patients.

Stock market response to COVID-19 pandemic: A comparative evidence from two emerging markets.

This paper presents the first comparative study of emerging stock markets' response to the COVID-19 pandemic with evidence from Ghana and Botswana. Using daily time-series data from March 1, 2020, to September 30, 2021, the study estimates parametric, semi-parametric and non-parametric models, and provides evidence to support the negative effects of the COVID-19 pandemic (i.e., the total number of reported COVID-19 cases and deaths) on the stock market performances of Ghana and Botswana. Interestingly, the study shows that the impact of the pandemic on Ghana's stock market is quantitatively greater than the stock market of Botswana. The study calls for fiscal and monetary policies to help firms on the stock market to survive the shock. Going forward, measures aimed at building a robust stock market to withstand such external shocks are critical.

Improved seagull optimization algorithm of partition and XGBoost of prediction for fuzzy time series forecasting of COVID-19 daily confirmed.

The establishment of fuzzy relations and the fuzzification of time series are the top priorities of the model for predicting fuzzy time series. A lot of literature studied these two aspects to ameliorate the capability of the forecasting model. In this paper, we proposed a new method(FTSOAX) to forecast fuzzy time series derived from the improved seagull optimization algorithm(ISOA) and XGBoost. For increasing the accurateness of the forecasting model in fuzzy time series, ISOA is applied to partition the domain of discourse to get more suitable intervals. We improved the seagull optimization algorithm(SOA) with the help of the Powell algorithm and a random curve action to make SOA have better convergence ability. Using XGBoost to forecast the change of fuzzy membership in order to overcome the disadvantage that fuzzy relation leads to low accuracy. We obtained daily confirmed COVID-19 cases in 7 countries as a dataset to demonstrate the performance of FTSOAX. The results show that FTSOAX is superior to other fuzzy forecasting models in the application of prediction of COVID-19 daily confirmed cases.

Intraparenchymal fiberoptic intracranial pressure monitoring and decompressive craniectomy in meningioma case with critical intracranial pressure: A case report during COVID-19 pandemic.

Introduction: Meningioma is a slow-growing tumor that can cause neurological emergency due to intracranial hypertension. The definitive therapy is indeed emergency resection, but it is not always possible in several countries due to limited capacity and/or capability of the emergency operating room. The use of intraparenchymal fiberoptic intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in cases of brain tumors might be possible, but it is uncommon. We report a meningioma patient in whom immediate meningioma resection was considered too risky due to intensive care unit (ICU) shortage during COVID-19 pandemic and, therefore, underwent these procedures as life-saving measures. Case presentation: A 24-year-old man was brought to the emergency room with a chief complaint of seizure. Physical examination was notable for decreased consciousness (Glasgow Coma Scale (GCS) 11) and a dilated left pupil with intact light reflex. A contrasted Brain CT Scan revealed extra-axial mass on the left sphenoid with extensive tentacle edema, which pushed the midline structures 2 cm toward the contralateral side. Discussion: The patient was diagnosed with Left Sphenoid Meningioma. We decided to perform intraparenchymal fiberoptic ICP monitor insertion and DC considering the situation, device availability, safety, and efficacy. The patient slowly regained consciousness in the recovery room after the procedure. The best-observed GCS was 12. Two weeks afterward, the patient came back to our outpatient clinic neurologically intact. The patient was then planned for elective tumor resection. Conclusion: ICP monitoring and DC are not commonly performed on brain tumor cases. However, in suboptimal situations, these procedures might save lives. The present case showed that ICP monitor and DC were helpful in times of ICU shortage.

Roles of radiological technologists at Tsukuba Medical Examiner's Office equipped with a computed tomography system dedicated for the examination of corpses

The present study report introduces the roles of radiological technologists (RTs) at Tsukuba Medical Examiner's Office in Japan where a computed tomography system dedicated for examining corpses has been equipped. Several projects and enacted laws regarding postmortem imaging (PMI) have accelerated its use in many Japanese hospitals for detecting causes of death. The lack of sufficient forensic radiologists has led increasing need of RTs to assist forensic pathologists in a timely manner. Optimizing parameters and image processing of postmortem computed tomography (PMCT) and assistance in interpretation of PMCT using checklists by RTs help forensic pathologist to diagnose death causes and select needs for the following autopsy.

Application of a Non-Linear multi-model Ayurveda Intervention in elderly COVID-19 patients- a retrospective case series.

The COVID-19 pandemic is ravaging the world, leaving the mainstream medical system handicapped with no proven treatment at one end and the ambiguities regarding the efficacies of vaccines at the other. The elderly population is at greater risk in terms of complications and death. The use of complementary and alternative medicine (CAM) against COVID-19 has already been documented in countries like China with a national participation rate of 90%. In this regard, the practice of CAM especially Ayurveda is relevant in India. The current report is a case series of 64 elderly COVID-19 patients managed through a Non-Linear multi-modal Ayurveda Intervention (NLMAI) via online consultation. NLMAI is a combination of herbal and herbo-mineral drug interventions, lifestyle modifications, and psychological support done in 2 phases. The post-management analysis revealed a mean duration of 11 symptoms of COVID-19 assessed through survival function as 0.577 days [SE=0.39] with a CI of 95% [0.500-0.653] which was considerably low when compared to global statistics. Moreover, none of the cases advanced to complications or death. Hence, novel approaches like NLMAI can be utilized to counter the gravity of the COVID-19 after scientific validation.

Nature's therapy for COVID-19: Targeting the vital non-structural proteins (NSP) from SARS-CoV-2 with phytochemicals from Indian medicinal plants.

Background: Containing COVID-19 is still a global challenge. It has affected the "normal" world by targeting its economy and health sector. The effect is shifting of focus of research from life threatening diseases like cancer. Thus, we need to develop a medical solution at the earliest. The purpose of this present work was to understand the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained from our previous work, following drug-likeness properties, against 6 non-structural-proteins (NSP) from SARS-CoV-2. Methods: 100 ns molecular dynamics simulations were performed, and relative binding free energies were computed by MM/PBSA. Further, principal component analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to characterize protein-ligand interactions. Biological pathway enrichment analysis was also carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-CoV-2. Results: The potential binding modes and favourable molecular interaction profile of 9 phytochemicals, majorly from Withania somnifera with lowest free binding energies, against the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and 2 repurposed drugs with steroidal moieties in their chemical structures formed stable interactions with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were with the most significant p-value. Conclusions: To summarize this work, we suggest a global approach of targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative therapy for COVID-19. We also suggest that these phytochemicals need to be tested experimentally to confirm their efficacy.

Research on the mechanism of berberine in the treatment of COVID-19 pneumonia pulmonary fibrosis using network pharmacology and molecular docking.

Purpose Pulmonary fibrosis caused by COVID-19 pneumonia is a serious complication of COVID-19 infection, there is a lack of effective treatment methods clinically. This article explored the mechanism of action of berberine in the treatment of COVID-19 (Corona Virus Disease 2019, COVID-19) pneumonia pulmonary fibrosis with the help of the network pharmacology and molecular docking. Methods We predicted the role of berberine protein targets with the Pharmmapper database and the 3D structure of berberine in the Pubchem database. And GeneCards database was used in order to search disease target genes and screen common target genes. Then we used STRING web to construct PPI interaction network of common target protein. The common target genes were analyzed by GO and KEGG by DAVID database. The disease-core target gene-drug network was established and molecular docking was used for prediction. We also analyzed the binding free energy and simulates molecular dynamics of complexes. Results Berberine had 250 gene targets, COVID-19 pneumonia pulmonary fibrosis had 191 gene targets, the intersection of which was 23 in common gene targets. Molecular docking showed that berberine was associated with CCl2, IL-6, STAT3 and TNF-α. GO and KEGG analysis reveals that berberine mainly plays a vital role by the signaling pathways of influenza, inflammation and immune response. Conclusion Berberine acts on TNF-α, STAT3, IL-6, CCL2 and other targets to inhibit inflammation and the activation of fibrocytes to achieve the purpose of treating COVID-19 pneumonia pulmonary fibrosis.

Natural products as a source of novel drugs for treating SARS-CoV2 infection.

COVID-19, the infectious disease caused by the beta-corona virus SARS-CoV2, has posed a global health threat causing more than five million of deaths in the last two years in the world. Although the disease often presents with mild cold-like symptoms, it may have lethal consequences following thromboembolisms, hyperinflammation and cytokine storm eventually leading to pulmonary fibrosis and multiple organ failure. Despite the progress made in the understanding of the SARS-CoV2 pathology and the clinical management of COVID-19, the viral illness is still a health concern since outbreaks continue to resurge due to the emergence of mutant variants of the virus that resist the vaccines. Therefore, there is an urgent need for therapeutics that can block SARS-CoV2 viral transmission and the progression from infection to severe symptomatic illness. Natural products could be a valuable source of drugs for the management of COVID-19 disease, particularly because they can act on multitargets and through different mechanisms including inhibition of biochemical pathways, epigenetic regulation of gene expression, modulation of immune response, regulation of pathophysiological stress response. Here we present an overview of the natural products that possess SARS-CoV2 antiviral activity and the potential to benefit the management of COVID-19.

Emergence, evolution, and vaccine production approaches of SARS-CoV-2 virus: Benefits of getting vaccinated and common questions.

The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, ßCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.

Transmission Dynamics of Coronavirus Disease 2019 Based on "Virus Variants" and "Environment-to-human"

Recently, "environment-to-human" transmission has become a new pattern in the spread of COVID-19, and novel coronavirus variants with increased infectivity have appeared in many countries. With considering the "environment-to-human" transmission and virus mutations of the novel coronavirus, the SEIQR model of infectious disease dynamics was established to simulate the development trend of the epidemic. The results showed that, the increased infectivity of virus variants and "environment-to-human" transmission positively affects the spread and speed of COVID-19 epidemic, in which the virus variants had a more significant impact, and the "environment-to-human" transmission will promote the outbreak time of the epidemic to be greatly advanced. For the virus variants with higher infectivity, elevating the intensity of interventions has a more remarkable effect on controlling the spread of COVID-19 variants. © 2021, The Editorial Department of Complex Systems and Complexity Science. All right reserved.

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis.

Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits (2-22) with better binding energy than remdesivir (1), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits (2 and 3) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

"SARS-CoV-2 Infection in Liver Transplant Recipients - Immunosuppression is the Silver Lining?"

BACKGROUND: COVID-19 is associated with higher mortality among patients who have comorbidities. However, evidences related to COVID-19 among post liver transplant recipients are scarce and evolving. METHODS: Adult Indian patients who had undergone liver transplantation at our centre since 2006 and were under regular follow-up, were contacted either telephonically or on email. Data were recorded related to symptoms and diagnosis of COVID-19, need for hospitalization, and need for ICU stay and mortality. RESULTS: Eighty one (3.71%) of the 2182 adult Liver transplant (LT) recipients on regular follow-up reported SARS-CoV-2 infection between 1st April 2020 and 31st May 2021. Mean age was 51.3(±9.8) years, and 74(91.4%) were males. Thirty five (43.2%) patients had one or more comorbidities. Twenty one (25.9%) patients were transplanted less than 1 year ago. Forty four (54.3% ) patients had mild disease only while 23(28.4%) patients had severe COVID-19 disease. Of the 81 patients 14 patients died and overall mortality was 17.3. CONCLUSION: Uncomplicated liver transplant recipients without comorbidities who acquire SARS-CoV-2 do not have poor outcome.